Finding and Treating Unsuspected and Resistant TB to Reduce Hospital Transmission

描述（由申请人提供）：耐多药结核病威胁着全球结核病控制，传播导致了一半以上的病例。医院和其他聚集场所是结核病传播的常见焦点，包括向患者和卫生保健工作者传播。在多药和广泛耐药结核病和艾滋病毒时代，结核病在医院传播的后果是致命的。除了发病率、死亡率和医疗费用外，卫生保健工作者中的活动性结核病还导致劳动力减员，并进一步使患者暴露于感染。长期存在的证据表明，传播并非来自接受有效治疗的结核病患者，而是来自未被怀疑的病例以及未被怀疑具有耐药性的已知病例。全面的国际指南鼓励早期诊断，但往往侧重于已知和疑似病例、环境控制和个人呼吸保护。迫切需要在医院和其他人群聚集的环境中采取一种根本不同的结核病控制方法。近年来，出现并正在实施结核病和耐药性的快速分子检测。本提案调查了在结核病流行环境中繁忙的城市医院实施一种名为FAST（基于分子药敏试验积极发现病例、暂时隔离和有效治疗）的结核病传播控制重新聚焦方法的情况。除了研究基于痰的快速分子诊断测试外，该研究还将评估一种新型的结核病呼气测试是否可以通过可靠地排除结核病而避免对痰测试的需要。与此同时，

DESCRIPTION (provided by applicant): Multidrug resistant tuberculosis threatens global TB control, and transmission is responsible for more than half of all cases. Hospitals and other congregate settings are common foci of TB transmission, including spread to patients and health care workers. In the era of multidrug and extensively drug resistant TB and HIV, the consequences of TB transmission in hospitals are deadly. In addition to the morbidity, mortality and medical costs, active TB in health care workers also leads to workforce attrition and further exposes patients to infection. There is longstanding evidence that transmission is not from TB patients on effective treatment, but from unsuspected cases, and known cases with unsuspected drug resistance. Comprehensive international guidelines encourage early diagnosis, but tend to focus on known and suspected cases, environmental controls, and personal respiratory protection. A fundamentally different approach to TB control in hospitals and other congregate settings is urgently needed. In recent years, rapid molecular tests for TB and drug resistance have emerged and are being implemented. This proposal investigates the implementation of a refocused approach to TB transmission control called FAST (Find cases Actively, Separate temporarily, and Treat effectively based on molecular drug susceptibility testing) in a busy, urban hospital in a TB endemic setting. In addition to the investigation of rapd sputum based molecular diagnostic tests, the study will evaluate whether a novel, exhaled breath test for TB can avoid the need for sputum testing by reliably excluding TB. In parallel, the study will investigate the adoption of annual tuberculin skin testing (TST) of health care workers at the hospital to measure the impact of FAST on transmission. The analyses will incorporate the RE-AIM framework to identify the critical elements of the programs that will enhance the reach, effectiveness, adoption, implementation, and maintenance of these strategies in other hospitals. Three specific aims are proposed. The first aim is to evaluate FAST for reducing treatment delay and health care workers infections. The second aim is to evaluate the acceptability and barriers to FAST and health care worker TST. The third aim is to compare the cost and cost- effectiveness of FAST relative to smear and culture for TB diagnosis, drug resistance testing, and treatment initiation. The proposed research is significant because it seeks to create safer health care facilities in high- burden, resource-limited settings by reducing TB transmission to health care workers and patients. It is innovative because it shifts the focus of hospital based TB control to active case finding and prompt treatment of patients with unsuspected pulmonary TB and unsuspected drug resistance.